In the 2-year AFFIRM pivotal trial:

Relapsing MS patients received 300 mg TYSABRI IV every 28 days (n=627) or placebo (n=315). Patients with PPMS, SPMS, and PRMS were excluded.

83% of patients taking TYSABRI had no sustained physical disability progression for 12 weeks vs 71% with placebo (primary endpoint: 17% vs 29%; p<0.001)1,2

HEALTH-RELATED QUALITY OF LIFE WAS ANALYZED IN PATIENTS AFTER TREATMENT WITH TYSABRI

In an exploratory analysis of the pivotal trials:

TYSABRI patients reported improved health-related quality of life (HRQoL) scores3

Study description: A retrospective, exploratory analysis of the pivotal trials was performed to report the effects of TYSABRI on HRQoL as measured by the Short Form-36 (SF-36). Annualized relapse rate (ARR) was measured at 3-month intervals.3,a,b,c

  • The SF-36 is a widely used, general HRQoL instrument that contains 36 items used to assess patients’ health status and its impact on their lives

Study limitations:

  • Results are exploratory outcomes of the AFFIRM trial, and a number of calculations were made to evaluate data trends; therefore, marginal p values should be interpreted with caution
  • The standard minimally important difference cutoff of 5 points was derived from a disease-free population, thus it may be preferable to establish a minimally important difference in patients with RMS
  • Significance level for testing the difference between treatment groups was set at 0.05 with no correction for multiple analyses
  • HRQoL measures were completed at baseline, and Weeks 24, 52, and 104. Earlier measures would have allowed better understanding of when patients might expect improvement after they start therapy, and testing between Weeks 52 and 104 would have provided insight into the stability of HRQoL benefits during the second year of treatment
  • HRQoL for 9% (8% TYSABRI, 10% placebo) of patients who withdrew from the study was not known. Reasons for discontinuation of TYSABRI were not collected 

HRQoL improvements were observed with TYSABRI as early as 6 months and sustained out to 2 years3

MEAN CHANGE FROM BASELINE IN INDIVIDUAL SCORES OF SF-36
Scale Baseline Week 24 Week 52 Week 104
TYSABRI Placebo TYSABRI Placebo TYSABRI Placebo TYSABRI Placebo
Physical Function 70.2 72.9 1.29d -2.17 1.70d -2.59 1.21f -5.17
Role-Physical 55.0 57.0 8.15d 0.84 7.38 1.74 6.81d -1.98
Bodily Pain 73.0 74.0 -0.28 -1.65 -0.37 -2.86 -0.96 -1.87
General Health 53.7 54.0 2.33 0.18 3.69e 1.03 3.82d -0.66
Vitality 48.3 52.9 3.03d -2.04 3.57 -0.32 3.74d -2.68
Social Function 71.4 73.8 2.07 -1.30 3.80 -0.34 4.03f -3.30
Role-Emotional 66.9 67.9 3.93 1.70 6.14 3.30 6.81f -2.73
Mental Health 67.0 69.2 1.41 -1.19 2.35 0.57 2.37 -0.09

Adapted from the American Medical Association by Wiley-Liss, Inc.
Bold rows with highlighted values: statistically significant compared with placebo.
Baseline scores and changes from baseline at Weeks 24, 52, and 104 are shown for all SF-36 scales.

  • After 2 years, TYSABRI treatment resulted in a significant improvement in the Physical Function, Role-Physical, General Health, Vitality, Social Function, and Role-Emotional scales of the SF-36

Physical Function score was significantly greater at 6 months, 1 year, and 2 years (p <0.01), and there were significant improvements in 6 of 8 individual HRQoL scales

Patients treated with TYSABRI reported mean improvements of >5 points relative to placebo in a majority of scales by Year 23

Mean Change from Baseline in Individual SF-36 Scale Scores at year 2
Mean Change from Baseline in Individual SF-36 Scale Scores at year 2

The improvement of 5.0 points (SD, 0.5) in TYSABRI-treated patients was considered a clinically meaningful differenceg

Patients taking TYSABRI achieved significant improvements in the Physical Function, Role-Physical, General Health, Vitality, Social Function, and Role-Emotional scales at 2 years3

EDSS=Expanded Disability Status Scale; MRI=magnetic resonance imaging; VAS=visual analog scale; PCS=Physical Component Summary; MCS=Mental Component Summary; SD=standard deviation.
 

aThe AFFIRM (NAtalizumab Safety and EFFlcacy in Relapsing-Remitting MS) study was a pivotal 2-year, double-blind, randomized, controlled trial with 942 relapsing MS patients who received either TYSABRI monotherapy (300 mg by intravenous infusion [n=627]) or placebo (n=315) every 4 weeks for up to 28 months (30 infusions), which excluded patients with primary progressive, secondary progressive, or progressive relapsing MS.1-3

bThe SENTINEL (Safety and Efficacy of NaTalizumab in Combination with INterferon Beta-1a in Patients With RELapsing Remitting Multiple Sclerosis): a pivotal 2-year, double-blind, placebo-controlled, parallel-group, randomized trial with relapsing MS patients who experienced one or more relapses while on treatment with interferon beta-1a (IFN-β-1a). Patients received either 300 mg TYSABRI (n=589) or placebo (n=582) every 4 weeks for up to 28 months, all patients continued to receive IFN-β-1a 30 μg IM once weekly, excluding patients with primary progressive, secondary progressive, or progressive relapsing MS.1,3,4

cThe SF-36 is a widely used, general HRQoL instrument that contains 36 items that assess patients’ health status and its impact on their lives. SF-36 HRQoL results are patient-reported.3

dp<0.01.

ep<0.05.

fp<0.001.

gThe standard minimally important difference cutoff of 5 points was used here (derived from the reference population of disease-free individuals). It may be preferable to establish a minimally important difference in patients with RMS.3